Delany-Moretlwe Sinead, Hanscom Brett, Guo Xu, Nkabiito Clemensia, Mandima Patricia, Nahirya Patricia Ntege, Mpendo Juliet, Bhondai-Mhuri Muchaneta, Mgodi Nyaradzo, Berhanu Rebecca, Farrior Jennifer, Piwowar-Manning Estelle, Ford Susan L, Hendrix Craig W, Rinehart Alex R, Rooney James F, Adeyeye Adeola, Landovitz Raphael J, Cohen Myron S, Hosseinipour Mina C, Marzinke Mark A
Wits RHI, University of the Witwatersrand, Johannesburg, South Africa.
Statistical Centre for HIV/AIDS Research Prevention Fred Hutchinson Cancer Research Institute, Seattle, Washington, USA.
J Int AIDS Soc. 2025 Jan;28(1):e26401. doi: 10.1002/jia2.26401.
Long-acting injectable cabotegravir (CAB-LA) for pre-exposure prophylaxis significantly reduced HIV acquisition in HPTN 084. We report on the safety and CAB-LA pharmacokinetics in pregnant women during the blinded period of HPTN 084.
Participants were randomized 1:1 to either active cabotegravir (CAB) plus tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) placebo or active TDF/FTC plus CAB placebo. Pregnancy testing was performed at each visit; participants with a positive test had study product withheld and were offered open-label TDF/FTC. Pregnancies were confirmed on two tests at least 4 weeks apart. All participants with a positive pregnancy test prior to November 5, 2020 are included in this analysis. Pregnancy incidence, maternal adverse event (AE) incidence, pregnancy outcomes (including composite outcome of spontaneous abortion <20 weeks, intrauterine foetal death or stillbirth ≥20 weeks, premature birth <37 weeks, or small for gestational age) were assessed. The apparent terminal phase half-life (t) of CAB-LA in pregnant women in HPTN 084 was compared to non-pregnant women from the phase 2a HPTN 077 trial. Multivariable models assessed associations with t RESULTS: Fifty-seven pregnancies (30 CAB-LA, 27 TDF/FTC) were confirmed over 3845 person-years [py] (incidence 1.5/100 py, 95% CI 1.1-1.9). CAB-LA group participants had a median 342 days (IQR 192, 497) of CAB-LA exposure prior to pregnancy detection. Grade 2 or higher maternal AE incidence did not differ by study arm (CAB 157, 95% CI 91-271 per 100 py vs. TDF/FTC 217, 95% CI 124-380 per 100 py; p = 0.256). Most pregnancies (81%) resulted in live births (25 CAB-LA, 22 TDF/FTC). Composite poor pregnancy outcomes did not differ significantly by group (CAB 6/30 vs. TDF/FTC 4/27; p = 0.476). No congenital anomalies were observed. The CAB t geometric mean was 52.8 days (95% CI 40.7-68.4) in pregnant women compared to 60.3 days (95% CI 47.7-76.3; p = 0.66) in non-pregnant women; neither pregnancy nor body mass index were significantly associated with t.
CAB-LA concentrations post-cessation of injections were generally well tolerated in pregnant women. The t was comparable between pregnant and non-pregnant women. Ongoing studies will examine the safety and pharmacology of CAB-LA in women who choose to continue CAB-LA through pregnancy and lactation.
长效注射用卡博特韦（CAB-LA）用于暴露前预防可显著降低HPTN 084研究中HIV的感染率。我们报告了在HPTN 084的盲法研究期间，孕妇使用CAB-LA的安全性和药代动力学情况。
参与者按1:1随机分为接受活性卡博特韦（CAB）加替诺福韦酯/恩曲他滨（TDF/FTC）安慰剂组，或活性TDF/FTC加CAB安慰剂组。每次访视时进行妊娠检测；检测呈阳性的参与者停用研究药物，并提供开放标签的TDF/FTC。妊娠通过至少间隔4周的两次检测得以确认。本分析纳入了2020年11月5日前妊娠检测呈阳性的所有参与者。评估妊娠发生率、母体不良事件（AE）发生率、妊娠结局（包括妊娠<20周自然流产、≥20周宫内胎儿死亡或死产、<37周早产或小于胎龄儿的复合结局）。将HPTN 084研究中孕妇的CAB-LA表观终末相半衰期（t）与2a期HPTN 077试验中的非孕妇进行比较。多变量模型评估与t的相关性。
在3845人年[py]中确认了57例妊娠（30例CAB-LA组，27例TDF/FTC组）（发生率1.5/100 py，95%CI 1.1-1.9）。CAB-LA组参与者在妊娠检测前接受CAB-LA的中位时间为342天（IQR 192，497）。2级或更高级别的母体AE发生率在各研究组间无差异（CAB组每100 py为157例，95%CI 91-271例；TDF/FTC组每100 py为217例，95%CI 124-380例；p = 0.256）。大多数妊娠（81%）以活产告终（CAB-LA组25例，TDF/FTC组22例）。复合不良妊娠结局在两组间无显著差异（CAB-LA组6/30例 vs. TDF/FTC组4/27例；p = 0.476）。未观察到先天性异常。孕妇的CAB t几何均值为52.8天（95%CI 40.7-68.4），非孕妇为60.3天（95%CI 47.7-76.3；p = 0.66）；妊娠和体重指数均与t无显著相关性。
孕妇在停止注射后CAB-LA浓度总体耐受性良好。孕妇和非孕妇的t相当。正在进行的研究将考察选择在妊娠和哺乳期继续使用CAB-LA的女性中CAB-LA的安全性和药理学情况。
